Abstract

5736

CD30 is a member of the tumor necrosis factor receptor superfamily. Overexpression of CD30 on some neoplasms versus limited expression on normal tissues makes this receptor a promising target for antibody-based therapy. Alpha particles are very attractive for cancer therapy, especially for isolated malignant cells as is observed in leukemia, because of their high linear energy transfer and short effective path length in tissues. In this study, we evaluated the therapeutic efficacy of the 211At labeled anti-CD30 monoclonal antibody HeFi-1 alone and its combination with unmodified HeFi-1 in a murine model of human anaplastic large cell lymphoma. The tumor model was established by i.v. injection of 1x107 karpas299 cells into SCID/NOD mice. Unmodified HeFi-1 given at 100 μg weekly for 4 weeks significantly prolonged the survival of the karpas299 bearing mice as compared with the controls (p<0.01). A single dose of 12 μCi of 211At-HeFi-1 showed greater therapeutic efficacy than unmodified HeFi-1 as shown by survival of the mice (p<0.01). Combination of the two agents with different mechanisms of action resulted in an enhanced antitumor effect, as shown by survival of the mice, when compared with the groups treated either with 211At-HeFi-1 (p<0.05) or with unmodified HeFi-1 (p<0.01). The median survival duration of the control group was 27 days and it was prolonged to 50 days in the HeFi-1 group, 114 days in the 211At-HeFi-1 group, respectively. All mice in the control group died by day 66, and by day 80 in the HeFi-1 group. In contrast, 33% of the mice in the 211At-HeFi-1 group and 83% in the combination group survived greater than 130 days. In summary, 211At-HeFi-1 and its combination with unmodified HeFi-1 are very promising for the treatment of CD30 expressing anaplastic large cell lymphoma and Hodgkin's disease.